Complement activation by the alternative pathway may provide an early host response to microorganisms and altered mammalian cells. A major function of the activating particle is to provide a site for the formation of the C3 convertase where the convertase is protected from inactivation by serum regulatory proteins. Changes in mammalian cell surfaces, such as removal of sialic acid from erythrocytes, can influence their ability to serve this protective function. We have found that model lipid membranes in the form of liposomes can activate complement by the alternative pathway, and that changes in composition affect this ability. Since the composition of the liposomes is defined and easily modified, they provide a simple model with which to study the role of membrane lipids in alternative pathway activation. We propose to characterize the membrane requirements for this activation by varying charge, phospholipid, cholesterol, fatty acid chain length and saturation, and presence of glycolipids in the membranes. We will then compare the abilities of liposomes of different composition to support the formation of active alternative pathway C3 convertase sites by purified components. The protective function of the liposomes will be compared by following the decay of C3b on the liposomes in the presence of serum regulatory proteins.